Polymorphisms of UGT1A7 and XRCC1 are Associated with an Increased Risk of Hepatocellular Carcinoma in Northeast China
Abstract
Objective:Hepatocellular carcinoma (HCC) is a complex disease which associates with both environmental and genetic factors. The purpose of this study was to investigate whether the genetic polymorphisms of UDPglucuronosyltransferase( UGT1A7), an important phase II biotransformation enzyme, and X-ray repair crosscomplementing group 1(XRCC1), a pivotal DNA-repair gene, were related to the risk of HCC in Northeast China.
Methods: One hundred and thirty six HCC patients and one hundred and thirty six frequency-matched controls were included in this hospital-based case-control study. Genotypes of UGT1A7 and XRCC1 were determined using allele-specific polymerase chain reaction (AS-PCR) and PCR-restriction fragment length polymorphism (RFLP), and for which the odds ratio (OR) with 95% confidence interval (95% CI) were calculated.
Results: The proportion of UGT1A7 low enzymatic allele (*2 or *3) was higher in HCC patients than those in controls. The UGT1A7*1/*2 and *3/*3 genotypes were associated with higher HCC risk (OR=2.09, 95%CI: 1.10-3.97; OR=5.67, 95%CI: 1.76-18.30, respectively). The XRCC1 codon 399 Arg/Gln genotype could also elevate HCC risk (OR=2.16, 95% CI 1.29-3.61). In addition to polymorphisms of UGT1A7 and XRCC1, multivariate logistic regression analysis demonstrated that other significant independent factors associated with HCC were HBV infection (OR=68.07, 95%CI: 28.03-165.26), HCV infection (OR=30.97, 95%CI: 8.06-118.94) and family history of HCC (OR=10.62, 95%CI: 2.22-50.77).
Conclusion: The study shows that the polymorphisms of UGT1A7 and XRCC1 are associated with HCC risk. Determination of the polymorphisms of UGT1A7 and XRCC1 may provide an important clue to preventive measure against HCC.
Methods: One hundred and thirty six HCC patients and one hundred and thirty six frequency-matched controls were included in this hospital-based case-control study. Genotypes of UGT1A7 and XRCC1 were determined using allele-specific polymerase chain reaction (AS-PCR) and PCR-restriction fragment length polymorphism (RFLP), and for which the odds ratio (OR) with 95% confidence interval (95% CI) were calculated.
Results: The proportion of UGT1A7 low enzymatic allele (*2 or *3) was higher in HCC patients than those in controls. The UGT1A7*1/*2 and *3/*3 genotypes were associated with higher HCC risk (OR=2.09, 95%CI: 1.10-3.97; OR=5.67, 95%CI: 1.76-18.30, respectively). The XRCC1 codon 399 Arg/Gln genotype could also elevate HCC risk (OR=2.16, 95% CI 1.29-3.61). In addition to polymorphisms of UGT1A7 and XRCC1, multivariate logistic regression analysis demonstrated that other significant independent factors associated with HCC were HBV infection (OR=68.07, 95%CI: 28.03-165.26), HCV infection (OR=30.97, 95%CI: 8.06-118.94) and family history of HCC (OR=10.62, 95%CI: 2.22-50.77).
Conclusion: The study shows that the polymorphisms of UGT1A7 and XRCC1 are associated with HCC risk. Determination of the polymorphisms of UGT1A7 and XRCC1 may provide an important clue to preventive measure against HCC.